Mechanism of miR-34a in the metabolism of extracellular matrix in fibroblasts of stress urinary incontinence via Nampt-mediated autophagy

• Published in: Cell stress & chaperones Vol. 27; no. 4; pp. 369 - 381
• Main Authors: Zhou, Ying, Li, Hongjuan, Wang, Lu
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Science + Business Media 01.07.2022; Springer Netherlands; Springer Nature B.V
• Subjects: Autophagy; Autophagy - genetics; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Biology; Cell culture; Extracellular matrix; Extracellular Matrix - metabolism; Female; Females; Fibroblasts; Fibroblasts - metabolism; Gelatinase A; Gelatinase B; Humans; Hygiene; IL-1β; Immunology; Interleukin 1; Matrix metalloproteinases; Metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neurosciences; Nicotinamide; Nicotinamide Phosphoribosyltransferase - genetics; Nicotinamide Phosphoribosyltransferase - metabolism; Original; ORIGINAL ARTICLE; Reporter gene; Ribonucleic acid; RNA; Tissue inhibitor of metalloproteinase 1; Urinary incontinence; Urinary Incontinence, Stress - genetics; Urinary Incontinence, Stress - metabolism; Vagina; Stress urinary incontinence; Extracellular matrix metabolism; miR-34a; Autophagy; Fibroblast; Nampt
• ISSN: 1355-8145; 1466-1268; 1466-1268
• DOI: 10.1007/s12192-022-01278-w

Stress urinary incontinence (SUI) is a troublesome hygienic problem that afflicts the female population and is associated with extracellular matrix (ECM). Herein, we investigated the effects of microRNA (miR)-34a on ECM metabolism in fibroblasts of SUI via mediating nicotinamide phosphoribosyl transferase (Nampt/NAmPRTase) and hope to find novel insights in the treatment of SUI. Firstly, the anterior vaginal wall tissues of SUI patients and the female vaginal wall fibroblasts (FVWFs) of non-SUI subjects were collected and identified. Then, FVWFs were treated with 10 ng/mL of interleukin 1 beta (IL-1ß) to establish SUI cell models. Subsequently, miR-34a and Nampt expressions in both types of cells were detected via RT-qPCR. It was found that miR-34a was poorly expressed, while Nampt was highly expressed in SUI. Subsequently, IL-1ß-treated FVWFs were transfected with miR-34a-mimic and pcDNA3.1-Nampt, respectively. Thereafter, RT-qPCR and Western blot detected that miR-34a overexpression increased COL1A, ACAN, and TIMP-1; decreased MMP-2 and MMP-9; and elevated LC3 II/I ratio, Beclin-1 expression, and the autophagosome number in IL-1ß-treated FVWFs, while Nampt upregulation reversed the above outcomes. Then, dual-luciferase reporter gene assay detected that Nampt is a downstream target of miR-34a. Together, miR-34a overexpression promoted autophagy, inhibited ECM degradation in IL-1ß-treated FVWFs, and ameliorated SUI via suppressing Nampt.